1-(2-叠氮基乙基)氮杂环庚烷 | 1175146-65-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 中文名称: 1-(2-叠氮基乙基)氮杂环庚烷
• 英文名称: 1-(2-azidoethyl)azepane
• 英文别名: N-(2-azidoethyl)-hexamethyleneimine
• CAS: 1175146-65-2
• 化学式: C₈H₁₆N₄
• 分子量: 168.242
• InChiKey: IHWCQVNBNDLEOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  17.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  丙醛二乙基乙缩醛 、 1-(2-叠氮基乙基)氮杂环庚烷 在 sodium ascorbate 、 copper(II) sulfate 作用下， 生成
  参考文献：
  名称：

  Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-α production in human whole blood

  摘要：

  Tpl2 (cot/MAP3K8) is an upstream kinase of MEK in the ERK pathway. It plays an important role in Tumor Necrosis Factor-alpha (TNF-alpha) production and signaling. We have discovered that 8-halo-4-(3-chloro-4-fluorophenylamino)-6-[(1H-[ 1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles (4) are potent inhibitors of this enzyme. In order to improve the inhibition of TNF-alpha production in LPS-stimulated human blood, a series of analogs with a variety of substitutions around the triazole moiety were studied. We found that a cyclic amine group appended to the triazole ring could considerably enhance potency, aqueous solubility, and cell membrane permeability. Optimization of these cyclic amine groups led to the identification of 8-chloro-4-(3-chloro-4-fluorophenylamino)-6-((1-(1-ethylpiperidin-4-yl)-1H-1,2,3-triazol- 4-yl) methylamino)quinoline-3-carbonitrile (34). In a LPS-stimulated rat inflammation model, compound 34 showed good efficacy in inhibiting TNF-alpha production. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.009
• 作为产物：
  描述：

  2-(环己亚氨基)乙基氯 在 sodium azide 、 四丁基碘化铵 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-(2-叠氮基乙基)氮杂环庚烷
  参考文献：
  名称：

  来自 DNA 编码的吲哚聚焦 Ugi 肽模拟物的 TEAD-YAP 相互作用抑制剂和 MDM2 结合剂。

  摘要：

  DNA 编码的组合合成提供了对特权分子结构周围化学空间的有效和密集覆盖。色氨酸的吲哚侧链在蛋白质-蛋白质相互作用的关键或“热点”区域中发挥着重要作用。基于 Ugi 四组分反应设计了一个 DNA 编码的组合拟肽文库，采用色氨酸模拟吲哚侧链探测靶蛋白表面。在化学稳定的六胸苷衔接寡核苷酸“hexT”上合成了几种拟肽，由 DNA 序列编码，并通过叠氮化物-炔烃环加成取代，产生 8112 个分子的文库。

  DOI：

  10.1002/anie.202006280

文献信息

• SELECTIVE ALPHA-7 NICOTINIC RECEPTOR AGONISTS AND METHODS FOR MAKING AND USING THEM
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20180244653A1

  公开（公告）日：2018-08-30

  In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.

  在另一种实施方式中，提供了对α7尼古丁乙酰胆碱受体（α7 nAChR）具有高亲和力的选择性激动剂，基于受体占据和响应的选择性尼古丁受体亚型和配体门控离子通道亚型的筛选方法，行为评估用于在施用东莨菪碱后逆转认知障碍，随时间增强记忆保留，包括表征和高效筛选受体亚型选择性的制备和使用方法的制药组合物和配方以及包括它们的装置，提供了具有高亲和力和选择性结合的替代抗1,2,3-三唑化合物，例如5-（1-（2-（哌啶-1-基）乙基）-1H-1,2,3-三唑-4-基）-1H-吲哚（“IND1”），5-（（喹啉-3-基）-1H-1,2,3-三唑-4-基）-1H-吲哚（“IND8”）和3-（4-羟基苯基-1,2,3-三唑-1-基）喹啉（“QND8”）。在另一种实施方式中，提供了制造产品，例如泵、装置、注射器等，其中包括本文提供的化合物、制药组合物或配方。
• Side chain impacts on pH- and thermo-responsiveness of tertiary amine functionalized polypeptides
  作者：Chunsheng Xiao、Yilong Cheng、Yu Zhang、Jianxun Ding、Chaoliang He、Xiuli Zhuang、Xuesi Chen

  DOI：10.1002/pola.27048

  日期：2014.3.1

  The systemic investigation of the structural impacts of side chains on the pH‐ and thermo‐responsiveness of tertiary amine functionalized poly(l‐glutamate)s (TA‐PGs) was carried out. The TA‐PGs polymers were effectively synthesized by Cu(I)‐catalyzed azide‐alkyne cycloaddition click reaction of azido tertiary amines with poly(γ‐propargyl‐l‐glutamate) (PPLG). Turbimetric measurements were performed

  侧链上的pH的结构影响的系统调查和叔胺官能化聚（热响应性升-谷氨酸）S（TA-的PGs）中的溶液中进行。通过铜（I）催化的叠氮基叔胺与聚（γ-炔丙基-l-谷氨酸）（PPLG）的叠氮化物-炔烃环加成点击反应有效合成了TA-PGs聚合物。进行了比浊法测量，以表征TA-PG在水溶液中的pH和温度诱导的相变，这表明该性质对氮的结构依赖性取代基团和1,2,3-三唑环与侧链中叔胺基团之间的“连接基”。详细地讲，TA-PG的pH响应特性基本上由侧链中N-取代基团的疏水性决定，pH转变点（pH t）随着N-取代基团疏水性的增加而降低，而TA PG的温度响应性受N取代基或“连接基”的影响。具有中等N取代胺基（例如DEA，PR和PD）或支链“连接子”（例如iso-丙烯和2-甲基丙烯基）更可能表达因pH值变化而调整的LCST型相变。这项研究揭示的这些结构-属性关系将有助于开发TA-PG在智能药物输送系统中的应用。©2013
• Selective alpha-7 nicotinic receptor agonists and methods for making and using them
  申请人：The Regents of the University of California

  公开号：US10308638B2

  公开（公告）日：2019-06-04

  In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.

  在另一个实施方案中，提供了对α7烟碱乙酰胆碱受体（α7 nAChR）具有高亲和力的选择性激动剂、基于受体占据和反应的烟碱受体亚型和配体门控离子通道亚型选择性的检测方法、在东莨菪碱治疗后逆转认知障碍的行为评估、随时间增强记忆保持、药物组合物和制剂及包含它们的装置，以及制造和使用它们的方法，包括表征和有效测定它们的受体亚型选择性。在另一种实施方案中，提供了对α7 尼古丁乙酰胆碱受体（α7 nAChR）具有高亲和力和选择性结合的取代抗 1,2,3-三唑化合物、例如 5-(1-(2-(哌啶-1-基)乙基)-1H-1,2,3-三唑-4-基)-1H-吲哚（"IND1"）、5-((奎宁环-3-基)-1H-1,2,3-三唑-4-基)-1H-吲哚（"IND8"）和 3-(4-羟基苯基-1,2,3-三唑-1-基)奎宁环（"QND8"）。在另一种实施方案中，提供了包含本文所提供的化合物、药物组合物或制剂的制造产品，如泵、装置、注射器等。
• Selectivity Optimization of Substituted 1,2,3-Triazoles as α7 Nicotinic Acetylcholine Receptor Agonists
  作者：Kuntarat Arunrungvichian、Valery V. Fokin、Opa Vajragupta、Palmer Taylor

  DOI：10.1021/acschemneuro.5b00058

  日期：2015.8.19

  Three series of substituted anti-1,2,3-triazoles (IND, PPRD, and QND), synthesized by cycloaddition from azide and alkyne building blocks, were designed to enhance selectivity and potency profiles of a lead alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR) agonist, TTIn-1. Designed compounds were synthesized and screened for affinity by a radioligand binding assay. Their functional characterization as agonists and antagonists was performed by fluorescence resonance energy transfer assay using cell lines expressing transfected cDNAs, alpha 7-nAChRs, alpha 4 beta 2-nAChRs, and 5HT(3A), receptors, and a fluorescence cell reporter. In the END series, a tropane ring of TTIn-1, substituted at Ni, was replaced by mono- and bicyclic amines to vary length and conformational flexibility of a carbon linker between nitrogen atom and Ni of the triazole. Compounds with a two-carbon atom linker optimized binding with K-d's at the submicromolar level. Further modification at the hydrophobic indole of TTIn-1 was made in PPRD and QND series by fixing the amine center with the highest affinity building blocks in the IND series. Compounds from IND and PPRD series are selective as agonists for the alpha 7-nAChRs over alpha 4 beta 2-nAChRs and 5HT(3A) receptors. Lead compounds in the three series have EC50's between 28 and 260 nM. Based on the EC50, affinity, and selectivity determined from the binding and cellular responses, two of the leads have been advanced to behavioral studies described in the companion article (DOI: 10.1021/acschemneuro.5b00059).